Methods for the production of 4-chloroacetoacetyl chloride 4-chloro-3-oxobutanoyl chloride) and esters obtained from 4-chloroacetoacetyl chloride are known in the art. In a specific process, the 4-chloroacetoacetyl chloride is obtained by reacting chlorine gas with diketene (4-methylideneoxetan-2-one).
The reaction takes place exothermally and therefore requires cooling. The reaction products are relatively sensitive to heat and the formation of undesired side products and decomposition is observed if temperature deviates locally or globally from a given range. For example, undesired reaction products may be regioisomers, such 2-chloroacetoacetyl chloride, or over-chlorinated products, such as di- or tri-halogenated compounds, such as 2,4-dichloroacetoacetyl chloride or 2,2,4-trichloroacetoacetyl chloride. Thus, it is difficult to determine efficient production conditions by which a high yield is achieved.
JP 113 824 suggests a process in which diketene is dissolved in a solvent and reacted in a column reaction vessel with chlorine under cooling. The chlorine gas is fed into the column in a continuous current or counter-current manner. However, selectivities of less than 90% are achieved.
A solvent-free process is disclosed by U.S. Pat. No. 4,468,356, according to which a diketene spray is continuously contacted with chlorine gas in a reaction zone at a temperature between 80° C. and 210° C. Subsequently, the intermediate product is subjected to an esterification reaction with ethanol. However, the overall yield is below 80% and thus relatively low, which is probably due to the exposure of the intermediate product to relatively high temperatures. Further, the reaction is carried out only with small amounts of starting compounds at a laboratory scale.
Reactions for the production of haloacetoacetic acids from diketene and chlorine on laboratory scale are disclosed in U.S. Pat. No. 3,950,412 and U.S. Pat. No. 3,701,803. In U.S. Pat. No. 4,473,508, the process of U.S. Pat. No. 3,701,803 is discussed. The inventors conclude that an upscale would not be possible because of problems associated with heat transfer. In order to provide an efficient reaction on increased scale, it is suggested to react a solution of diketene in an inert solvent with a solution of chlorine dissolved in an inert solvent in a tube reactor. According to Example 6, the acid chloride intermediate can be produced at a yield of 98%. However, the process is relatively inefficient, because both starting compounds are diluted in relatively large amounts of solvents. Thus, the overall reaction requires large amounts of solvent and consequently large reactors and equipment and more energy for cooling. When increasing the volume of the reactor, the yield dropped “drastically” and the selectivity was relatively low (U.S. Pat. No. 4,473,508, example 7). Thus it would be desirable to provide a more efficient process, which requires less solvent, is more selective and efficient on a large scale.
A laboratory process in order to produce ethyl-4-chloroacetoacetate from diketene and chlorine is disclosed by Pan et al., Shandong Huagong 2007, 36 (10) 4-6. In this process, it is suggested to use a relatively high concentration of diketene of about 24 to 28 weight-%. However, the yield of the ester is only about 80% and the reaction is carried out in a reaction flask on small scale, without any suggestion how to resolve the heat transfer problem on increased scale.
The processes known in the art are also problematic with respect to process safety. Especially when carried out in an industrial scale, the reaction requires high amounts of chlorine and diketene. These substances are highly reactive and hazardous when inhaled. When the reactor is damaged or when the process is disturbed and gets out of control, the reactants could harm the people in the environment and explode. Thus an industrial upscale, if at all, would only be possible under severe safety precautions.